Phase II Study of Orelabrutinib Combined With PD-1 Inhibitor in Relapsed/Refractory Primary Central Nervous System Lymphoma

Orelabrutinib Combined With PD-1 Inhibitor in Relapsed/Refractory Primary Central Nervous System Lymphoma: a Prospective Multi-center Phase II Study

This is a prospective multicenter single-arm phase II study, and the purpose of this study is to evaluate the efficiency of Orelabrutinib combined with PD-1 inhibitor regimen relapsed/refractory primary intraocular lymphoma. Overall response rate （ORR） after 4 cycles is the primary endpoint.

All the patients will be treated with Orelabrutinib combined with PD-1 inhibitor ：Orelabrutinib 150mg qd，Tislelizumab Injection 200mg d1 or Sintilimab injection 200mg d1， every 21-day for 1 cycle). Patients will be evaluated every 2 cycles by MRI scan during the first 6 cycles，and then the interval of investigation will be prolonged to 12 weeks. The patients who achieved complete remission (CR) or partial remission (PR) or stable disease (SD) will receive further treatment. The patients progressed disease (PD) will withdraw from the trial and receive salvage regimens. The treatment will be continued for 2 years or until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

During following-up, surveillance ophthalmologic examination and brain magnetic resonance imaging (MRI) scans can be performed every 3 months up for 2 years.

Inclusion Criteria:

• Age ≥18 years old ≤75 Years old, male or female
• Primary Central nerves system lymphoma confirmed by cytology or histology according to WHO2016 criteria
• No evidence of systemic lymphoma
• Patients with a clear diagnosis of relapsed and/or refractory PCNSL: they received at least one regimen containing methotrexate.
• At least one measurable lesion according to Lugano 2014 criteria
• Adequate organ function and adequate bone marrow reserve

Exclusion Criteria:

• Malignant tumors other than B-NHL within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery
• Active HIV, HBV, HCV or treponema pallidum infection
• Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy
• Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after their cell transfusion
• Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment
• Any systemic antitumor therapy performed within 2 weeks before enrollment
• Previous use of other BTK inhibitors or PD-1 inhibitors.